You are here:
Characterizing High Throughput Toxicokinetics for Chemical Decision Making
Citation:
Wambaugh, J., M. Beal, M. Devito, S. Ferguson, M. Hughes, R. Judson, I. Moffat, A. Nong, A. Paini, K. Paul-Friedman, R. Thomas, AND B. Wetmore. Characterizing High Throughput Toxicokinetics for Chemical Decision Making. ISES, Lisbon, N/A, PORTUGAL, September 25 - 29, 2022. https://doi.org/10.23645/epacomptox.21126658
Impact/Purpose:
This is a contributed abstract for the Internatinal Society of Exposure Science annual meeting. This year's topic is: From Exposure to Human Health: New Developments and Challenges in a Changing Environment.
Description:
Toxicokinetics provides critical information linking external chemical exposures to internal tissue concentrations, persistence in the body, and route of elimination. Unfortunately, most chemicals in commerce and the environment lack toxicokinetic data. Since 2017 a series of international workshops on Accelerating the Pace of Chemical Risk Assessment (APCRA) regularly have examined how new approach methodologies (NAMs) can transform the regulatory evaluation of chemicals. This APCRA case study describes a framework for decision makers to make use of high throughput toxicokinetics (HTTK). HTTK combines chemical-specific in vitro measures of TK with reproducible, transparent, and open-source TK models that place data generated by NAMs in a public health risk context and enhance interpretation of biomonitoring data. We are developing a tiered, two-dimensional framework that contrasts the decision context against chemical-specific considerations. Model complexity (for example, physiological processes described) is constrained by the limited data available to calibrate and test the TK models to justify assumptions and establish accuracy. Different levels of certainty are needed for prioritization, risk evaluation, and for protecting susceptible populations. We are organizing what can be measured and modeled with HTTK, while describing the decision context, applicable chemistry, scientific motivation, impact on models, and existence and appropriateness of quantitative structure-property relationship (QSPR) models. The resulting framework, examples, and check lists are intended to serve as a guide to regulators who are interested in knowing when and where HTTK might be used for chemical safety decision making. This abstract does not necessarily reflect any official agency or organization policy.
URLs/Downloads:
DOI: Characterizing High Throughput Toxicokinetics for Chemical Decision Making
ISES-APCRAHTTKCASESTUDY-WAMBAUGH-DRAFT6.PDF (PDF, NA pp, 2133.513 KB, about PDF)